Sharad D. Deodhar

Measurement of a monoclonal‐antibody‐defined antigen (CA 19‐9) in the sera of patients with malignant and nonmalignant diseases comparison with carcinoembryonic antigen

Immunoradiometric assay (IRMA) using monoclonal antibody for colon cancer cell surface antigen (CA19‐9) was compared with carcinoembryonic antigen (CEA) with regard to sensitivity and specificity in 730 patients. In the 341 patients who had no evidence of malignant disease, CA19‐9 levels ranged between <1.5 to 49 U/ml. Specificity of CA19‐9 at a cutoff of 20 U/ml was similar to that of CEA at a cutoff of 5.0 ng/ml; CA19‐9 was more sensitive than CEA in pancreatic cancer, whereas CEA was more sensitive than CA19‐9 in breast, colon, and gastric cancer. Of 17 patients with pancreatic cancer, 13 had elevated levels of CA19‐9 (sensitivity, 76%), whereas only 8 had elevated levels of CEA (sensitivity, 47%) and 15 had elevated levels of either CEA or CA19‐9 (sensitivity, 88%). These findings suggest that, like CEA, CA19‐9 is detectable in nonmalignant diseases and is not specific for gastrointestinal tumors, and has higher sensitivity than CEA only in pancreatic cancer. However, further prospective studies are required to verify its value in the diagnosis and management of pancreatic cancer.

Development of reticulum-cell sarcoma at the site of antilymphocyte globulin injection in a patient with renal transplant.

IMMUNOLOGIC mechanisms have an important surveillance role in detecting and destroying abnormal, potentially malignant cells arising either spontaneously or through the effect of various agents. Th...

Inhibition of liver metastases in murine colon adenocarcinoma by liposomes containing human C-reactive protein or crude lymphokine

SummaryPrevious studies from our laboratory have shown that liposomes containing LYNK or CRP inhibit lung metastases in mice bearing the malignant fibrosarcoma, T241. We have now extended these observations to the murine colon adenocarcinoma (MCA-38), which metastasizes to the liver. MCA-38 tumor cells (1×106) were implanted in the wall of the cecum by orthotopic transplantation. Three-hundred twenty-six mice bearing such tumors were divided into four treatment groups as follows: (1) no treatment (2) liposomes containing control medium (3) liposomes containing LYNK, and (4) liposomes containing CRP. Treatment was started from day 2, day 18, or 34 after tumor implantation and it was administered on 3 days per week. Each treatment, given parenterally, consisted of 4 μmol liposomes (PS-PC, 1:1) containing the appropriate agents. Mice receiving liposomes containing LYNK or CRP had significantly fewer and smaller liver metastases (25%–28%), than those in the two control groups (53%–54%). Also, a significantly better survival was noted in the two treated groups than in the two control groups. The most likely mechanism of tumor inhibition appears to be through macrophage activation. In the Winn tumor neutralization test, peritoneal macrophages harvested from normal mice 24 h after a single injection of liposomes (2.5 μmol) containing LYNK or CRP markedly inhibited tumor growth when a mixture of effector-target cells (40:1) was injected in the footpad. These studies further confirm the suggested role of CRP as an ‘immunomodulator’ or ‘biological response modifier’ in yet another tumor system.

Relapsing polychondritis: Immunomicroscopic findings in cartilage of ear biopsy specimens

Two cases of relapsing polychondritis are reported. Direct immunofluorescence examination of ear biopsy specimens in both patients showed the presence of granular deposits of immunoglobulins and the C3 component of complement at the chondrofibrous junction. These findings suggest that immunomicroscopic examination of ear cartilage could be diagnostically useful in this disease.

Microcytotoxicity and Serum Blocking Factors in Malignant Melanoma and Halo Nevus

Microcytotoxicity assays of patients with malignant melanoma and halo nevi were performed. No good correlation could be found between percent cell inhibition and histopathological level of melanoma or the clinical staging. The percent cell inhibition was usually an index of response to vaccinia virus immunotherapy. Actively regressing halo nevi showed high levels of percent cell inhibition, whereas inactive halo nevi had low levels of percent cell inhibition and blocking factor. Immunologic reactivity to melanoma cells may be a common feature of melanoma and halo nevus.

Study of the tumor cell-lymphocyte interaction in patients with breast cancer

The role of regional axillary node lymphocytes in the immune response to tumor cells in patients with breast cancer was studied in a tissue culture system in which the interaction between the tumor cells and lymphocytes was measured in terms of clumping of lymphocytes around tumor cells, their cytotoxic effect, and the blast transformation of lymphocytes; all these parameters were considered as evidence for cellular immune response to the tumor. Of the 17 patients studied in this manner, 10 who had no nodal or other metastatic involvement showed a significant tumor cell‐lymphocyte interaction, four who had extensive involvement of the axillary nodes showed no interaction, and, of the remaining three patients, in whom only one node appeared to be involved, two had a significant response whereas one showed no interaction. In six patients with no nodal involvement, both the nodal lymphocytes and the peripheral lymphocytes were available for studying the interaction with tumor cells, and, in all of these, the former showed a greater degree of reaction than the latter. The quantitative significance of this observation is not clear at the present time.

Role of preoperative irradiation in prolonging concomitant immunity and preventing metastasis in mice

As long as a primary allogeneic tumor was present on a mouses foot it sustained the concomitant immunity of the host and suppressed the growth of implants of the same tumor. A mouses immunity to reimplantation of the tumor waned perceptibly within 4 days of the time the tumor was removed, and by the seventh day was barely demonstrable. When the primary tumor was treated by a single large dose of irradiation, its cells, though doomed to die, either released large amounts of sensitizing antigens or continued for from 2 to 3 weeks to produce antigens and sustain the hosts immunity against reimplantations of the tumor. In an isogeneic tumor system, the incidence of pulmonary metastasis was much less after destruction of a tumor‐bearing foot by irradiation than when the foot was amputated. This suggests that even an isogeneic tumor confers some immunity on the host, and that the rapid waning of this immunity after amputation of the tumor‐bearing foot renders the host more susceptible to the development of metastases than it is following its destruction by irradiation.

In Vitro Assessment of Cell-mediated Immunity in Patients with Renal Cell Carcinoma

We evaluated 25 patients with renal cell carcinoma for cell-mediated immunity using the microtoxicity assay. Normal controls frequently exhibited significant cell inhibition. The mean percentage cell inhibition in patients after nephrectomy was significantly higher than in patients before nephrectomy and significantly higher than normal male subjects. No other correlation was found with respect to the stage of the disease. The incidence of significant autoblocking activity was noted more commonly in patients after nephrectomy than in patients before nephrectomy.

Activation of alveolar macrophage TNF and MCP-1 expression in vivo by a synthetic peptide of C-reactive protein.

Administration of multilamellar vesicles (MLV) encapsulating a synthetic peptide (RS‐83277) derived from human C‐reactive protein (CRP) augments anti‐tumor activity of murine alveolar macrophages and reduces established pulmonary metastases of experimental tumors. To explore mechanisms involved in these phenomena, we investigated cytokine and integrin (CD11b) expression of bronchoalveolar lavage (BAL)‐derived alveolar macrophages in control (blank MLV) and RS‐83277‐MLV‐treated C57B1 mice. Alveolar macrophage production of tumor necrosis factor α (TNF‐α) and monocyte chemoattractant bioactivity increased at 48 h after treatment with RS‐83277‐MLV but not control MLV. Chemoattractant activity was neutralized by antibody to monocyte chemoattractant protein‐1 (MCP‐1), but not irrelevant immunoglobulin G (IgG). Changes were reflected by augmented TNF‐α and MCP‐1 mRNA levels in pulmonary tissue and enhanced CD11b expression on mononuclear leukocytes derived from total lung tissue, but not on BAL‐derived alveolar macrophages. Results suggest that RS‐83277‐MLV treatment is associated with activation of alveolar macrophage TNF‐α and MCP‐1 production and up‐regulation of adhesion molecules on pulmonary mononuclear leukocytes but not on alveolar macrophages.

Immunotherapy of disseminated renal cell carcinoma with transfer factor.

Ten patients with disseminated renal cell carcinoma have been treated with transfer factor as an immunostimulant. In 5 patients with metastatic disease evident at the time of initial diagnosis treatment involved removal of the primary tumor followed by transfer factor therapy. Of these patients 3 had a temporary stabilization of metastatic disease. Three patients with recurrent metastatic disease after previous nephrectomy were treated, 2 of whom showed a temporary stabilization of metastatic disease. There were 2 additional patients without clinically evident metastases but at a high risk for recurrent disease who were treated and remain free of disease. We used 5 immunologic parameters to evaluate the clinical effects of transfer factor. No objective clinical regression was noted in any patient treated with measurable disease.